The work proposed is designed to test the following hypotheses: (1) The natural function of the stimulator cell (S-cell) in the mixed lymphocyte reaction is to stimulate T-cells in the presence of or after exposure to antigen. (2) All T-cell responses require the S-cell. (3) T-cells respond to novel patterns of transplantation antigen packing in the S-cell membrane produced by allelic Ir-genes or in response to antigen. Stimulator cells have been identified in three separate assays, the mixed lymphocyte reaction, the proliferative response to protein antigens and the antibody response to sheep red cells. In the latter assay the antigen to which T-cells are sensitized can be different from the B-cell antigen, and thus the factors determining stimulation of the two cells separated. The goal of this research is to determine whether the same stimulator cell is required for all three T-cell responses.